Our lab aims to understand mitochondrial biogenesis,
metabolism and RNA processing in trypanosomatid protozoa, which are important parasites of man and livestock,
and to
utilize that knowledge to inform drug development.

In particular, our studies currently focus on the following three areas:

Mitochondrial function in bloodstream stage trypanosomes

This project is aimed at shedding light on the essential - and
currently quite elusive - role that the mitochondrion plays in the
disease-causing (bloodstream) stage of trypanosomes. It also aims to
identify the adaptations that allow so-called dyskinetoplastic
trypanosomes to survive the loss of their mitochondrial genome, the
kinetoplast.

Trypanosome U insertion/deletion editing is a unique form of
post-transcriptional mRNA processing. It is catalyzed by a
macromolecular complex and of vital importance for the parasites. The
goal of this project is to determine the function of the various
editosome components, and how their activities are coordinated to
ensure precise editing.

RNA editing ligase as a novel drug target in trypanosomes

One of the key components of the editosome is RNA editing
ligase 1
(REL1). As a postdoc in Ken
Stuart's lab Achim has shown that it is an essential enzyme
in the
disease-causing stage of Trypanosoma
brucei and, in collaboration with Wim
Hol's lab
at the University of Washington in Seattle, determined its
three-dimensional structure. We are now using high throughput
biochemical screens as well as in
silico methods to identify REL1 inhibitors that can serve
as
starting points for drug development.